Association of MMP1 and MMP3 haplotypes with myocardial infarction and echocardiographic parameters of the left ventricle.

Tamara Djuric, Jovana Kuveljic, Ana Djordjevic, Milica Dekleva, Goran Stankovic, Aleksandra Stankovic, Maja Zivkovic

Molecular genetics & genomic medicine 2022 Sep

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Myocardial infarction (MI) leads to ischemia and afterward to left ventricular (LV) remodeling. Matrix metalloproteinase-1 (MMP1) and -3 (MMP3) belong to the family of endopeptidases and together they can dissolve most of the components of the extracellular matrix. MMP1 and MMP3 variants have been investigated solely in association with ischemic heart disease and LV dysfunction, but not in haplotype. The aims of this study were to investigate the association of haplotypes inferred from MMP1 rs1799750 (-1607 1G/2G; NC_000011.9:g.102670497del) and MMP3 rs35068180 (-1612 5A/6A; NC_000011.9:g.102715952dup) with MI and their effect on the change in echocardiographic parameters of LV structure and function in patients within 6 months after MI. The study included 325 patients with the first MI and 283 healthy controls. Gene variants were detected by PCR-RFLP method. Parameters of LV structure and function were assessed by conventional 2D echocardiography, 3-5 days and 6 months after the first MI, on a subgroup of 160 patients. Haplotype analysis was performed with Thesias software. Haplotypes 2G-5A and 1G-6A were significantly and independently associated with MI compared with the reference haplotype 2G-6A (adjusted, p = 0.009 and p = 0.026, respectively). After Bonferroni correction for multiple testing, MMP1 and MMP3 haplotypes lost their association with the change in LV long diameter and stroke volume within 6 months after MI. MMP1 and MMP3 haplotypes are strongly associated with MI. Further studies are needed to validate this result and to examine their association with echocardiographic parameters of LV structure and function after MI. © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

Citation

Tamara Djuric, Jovana Kuveljic, Ana Djordjevic, Milica Dekleva, Goran Stankovic, Aleksandra Stankovic, Maja Zivkovic. Association of MMP1 and MMP3 haplotypes with myocardial infarction and echocardiographic parameters of the left ventricle. Molecular genetics & genomic medicine. 2022 Sep;10(9):e2022